In this study, we investigated the effects of ingested water volume on the oral absorption of fenofibrate (FEN) with several formulations to confirm the applicability of rats for oral formulation screening. Oral absorption of suspended crystalline FEN was significantly improved by increasing ingested water volume (from 0.5 to 2 mL). FEN absorption improvement by particle size reduction and the linearity in oral absorption by dose escalation suggested that the rate-limiting step of FEN absorption in rats was the dissolution rate, consistent with that in humans. When FEN, as an amorphous solid dispersion (ASD) formulation, was suspended in water followed by immediate administration, oral FEN absorption was significantly higher than when administered in crystalline form and was not influenced by the differences in ingested water volume. Oral absorption of FEN from encapsulated ASD formulation in 1 or 2 mL of water was comparable with that of the suspension form. However, 0.5 mL of water significantly reduced the oral absorption of the solid ASD FEN formulation. These results indicate that to improve the oral absorption of poorly water-soluble drugs when performing a preclinical study with rats, 1 mL of water is the minimum preferable ingested volume to evaluate in vivo formulation performance.
Keywords: amorphous solid dispersion; fenofibrate; ingested water volume; micronized formulation; oral absorption; poorly water-soluble drug.